The human immunodeficiency viruses (HIV-1 and HIV-2), along with their simian counterpart, simian immunodeficiency virus (SIV), belong to the lentivirus family and are the etiological agents of acquired immune deficiency syndrome (AIDS). The regulation of HIV-1 and HIV-2 mRNA expression is determined by cis-regulatory sequences located in the long terminal repeat (LTR) region of the provirus. The HIV-1 LTR contains a core enhancer located at -79 to -109 bp, which has overlapping NFkappaB and ETS binding sites (EBS) (GGGACTTTCC) in a direct repeat configuration. An examination of promoters and enhancers that contain dual or multimeric EBS reveals that two distinct orientations exist for EBS: i) direct, in which the purine rich DNA strand has a linear, "head to tail" orientation, and ii) palindromic, in which the EBS are found to exist in a "head to head" orientation. The spacing between the two EBS cores in the HIV-1 enhancer is ten nucleotides, however, the distance between two EBS cores varies in different promoters.